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| These Usp18 (or Ubp43)-mutant mice may be useful in studying interferons and their receptors, cellular function, signal transduction, and the Janus kinase-signal transducer and activator of transcription (JAK-STAT) pathway. | |||||||||
- Description
- Phenotype
- Genes & alleles
- Genotyping
- Health & husbandry
- References
- Purchasing information
- Terms of Use
Description
Strain Information
Type Congenic; Mutant Strain; Targeted Mutation; Additional information on Genetically Engineered Mutant Mice. Mating System Homozygote x Homozygote (Female x Male) Species laboratory mouse Generation N11+N1 (18-JUL-08) Donating Investigator Dong-Er Zhang, The Scripps Research Institute Description
Homozygous Usp18 (or Ubp43) mutant mice on the FVB/N genetic background are viable and fertile, exhibiting none of the severe neurologic disorders that lead to embryonic lethality or early death reported for Ubp43-deficient mice on a C57BL/6 or mixed B6;129 genetic background. In contrast to wildtype mice, thymi from homozygous mice injected with LPS exhibit no protein from the targeted gene. Expression of the lacZ cassette is observed in both heterozygous and homozygous brain tissues. Homozygous mice are hypersensitive to type I interferon (IFN) and undergo apoptosis upon IFN stimulation. Ubp43-deficiency results in enhanced and prolonged STAT1 phosphorylation, DNA binding, and increased induction of hundreds of interferon stimulated genes (ISGs). Homozygous mice exhibit greater resistance to the cytopathic effects caused by a number of viruses (including lymphocytic choriomeningitis virus (LCMV), vesicular stomatitis virus (VSV), and Sindbis virus (SNV)). Ubp43-deficient cells exhibit high levels of ISG15 modified proteins. These Usp18 (or Ubp43)-mutant mice may be useful in studying interferons and their receptors, cellular function, signal transduction, and the Janus kinase-signal transducer and activator of transcription (JAK-STAT) pathway.In an attempt to offer alleles on well-characterized or multiple genetic backgrounds, alleles are frequently moved to a genetic background different from that on which an allele was first characterized. It should be noted that the phenotype could vary from that originally described. We will modify the strain description if necessary as published results become available.
Development
A targeting vector was designed to replace exons 2-4 of the targeted gene with a lacZ and PGK-neo cassette. The construct was electroporated into (129X1/SvJ x 129S1/Sv)F1-derived R1 embryonic stem (ES) cells. Correctly targeted ES cells were injected into blastocysts and chimeric mice were bred with C57BL/6 to produce mutant mice. Next, these mice were backcrossed to FVB/N inbred mice for at least 10 generations prior to arrival at The Jackson Laboratory.
Control Information
| Control | ||
|---|---|---|
| 001800 FVB/NJ | ||
| Considerations for Choosing Controls | ||
Related Strains
lacZ Expression Strains
View lacZ Expression Strains (175 strains)
Additional Web Information
Congenic Nomenclature
Fluorescent Proteins/lacZ Systems
Phenotype
Phenotype Information
assigned by genotype
The following phenotype information may relate to a genetic background differing from this JAX® Mice strain.
Usp18tm1Dzh/Usp18tm1Dzh
involves: 129S1/Sv * 129X1/SvJ
- life span-post-weaning/aging
- premature death (MGI Ref ID J:78821)
- behavior/neurological phenotype
- circling (MGI Ref ID J:78821)
- tight circling
- convulsive seizures (MGI Ref ID J:78821)
- spinning (MGI Ref ID J:78821)
- described as rolling
- tremors (MGI Ref ID J:78821)
- cardiovascular system phenotype
- intracerebral hemorrhage (MGI Ref ID J:78821)
- bloody cerebrospinal fluid was noted
- nervous system phenotype
- abnormal cerebral cortex morphology (MGI Ref ID J:78821)
- thinned cerebral cortex
- convulsive seizures (MGI Ref ID J:78821)
- enlarged lateral ventricles (MGI Ref ID J:78821)
- bilateral enlargement of lateral ventricle and third ventricle
- enlarged third ventricle (MGI Ref ID J:78821)
- bilateral enlargement of lateral ventricle and third ventricle
- hydroencephaly (MGI Ref ID J:78821)
- hydroencephaly first appears at postnatal day 14
- intracerebral hemorrhage (MGI Ref ID J:78821)
- bloody cerebrospinal fluid was noted
- hearing/vestibular/ear phenotype
- circling (MGI Ref ID J:78821)
- tight circling
This mouse can be used to support research in many areas including:
Cancer Research
Growth Factors/Receptors/Cytokines
Cell Biology Research
Signal Transduction
Developmental Biology Research
Perinatal Lethality (Homozygous)
Hematological Research
Immunological Defects
Immunology and Inflammation Research
CD Antigens, Antigen Receptors, and Histocompatibility Markers (genes regulating susceptibility to infectious disease and endotoxin)
Growth Factors/Receptors/Cytokines
Intracellular Signaling Molecules
Lymphoid Tissue Defects
Neurobiology Research
lacZ expression in neural tissue
Research Tools
lacZ Expression
Genetics Research (Tissue/Cell Markers: multiple)
Genetics Research (Tissue/Cell Markers: neurons)
Immunology and Inflammation Research (genes regulating susceptibility to infectious disease and endotoxin)
Neurobiology Research (cell marker)
Virology Research
Genes & Alleles
Gene & Allele Information
| Allele Symbol | Usp18tm1Dzh | ||
|---|---|---|---|
| Allele Name | targeted mutation 1, Dong-Er Zhang | ||
| Allele Type | Targeted (Reporter) | ||
| Common Name(s) | UBP43-/-; | ||
| Mutation Made By | Dong-Er Zhang, The Scripps Research Institute | ||
| Strain of Origin | (129X1/SvJ x 129S1/Sv)F1-Kitl<+> | ||
| ES Cell Line Name | R1 | ||
| ES Cell Line Strain | (129X1/SvJ x 129S1/Sv)F1-Kitl<+> | ||
| Site of Expression | Expression of lacZ is observed in brain tissues (expression in the ependymal cells of both the aqueduct and the ventricle). | ||
| Gene Symbol and Name | Usp18, ubiquitin specific peptidase 18 | ||
| Chromosome | 6 | ||
| Gene Common Name(s) | 1110058H21Rik; AW047653; ISG43; RIKEN cDNA 1110058H21 gene; UBP43; expressed sequence AW047653; | ||
| Molecular Note | Exons 2-4, which contain the translation initiation codon and Cys domain, were replaced with a neo-lacZ cassette via homologous recombination. Absence of gene expression in homozygous mutant animals was verified by Western blot analysis of LPS-stimulatedthymus glands. [MGI Ref ID J:78821] | ||
Genotyping
Genotyping Information
Genotyping Protocols
Usp18tm1Dzh, SEP PCR, vers. 1
Helpful Links
Optimizing PCR Protocols
References
References
Selected Reference(s)
Malakhova OA; Kim KI; Luo JK; Zou W; Kumar KG; Fuchs SY; Shuai K; Zhang DE. 2006. UBP43 is a novel regulator of interferon signaling independent of its ISG15 isopeptidase activity. EMBO J 25(11):2358-67. [PubMed: 16710296] [MGI Ref ID J:109574]
Ritchie KJ; Malakhov MP; Hetherington CJ; Zhou L; Little MT; Malakhova OA; Sipe JC; Orkin SH; Zhang DE. 2002. Dysregulation of protein modification by ISG15 results in brain cell injury. Genes Dev 16(17):2207-12. [PubMed: 12208842] [MGI Ref ID J:78821]
Additional References
Usp18tm1Dzh relatedGiannakopoulos NV; Luo JK; Papov V; Zou W; Lenschow DJ; Jacobs BS; Borden EC; Li J; Virgin HW; Zhang DE. 2005. Proteomic identification of proteins conjugated to ISG15 in mouse and human cells. Biochem Biophys Res Commun 336(2):496-506. [PubMed: 16139798] [MGI Ref ID J:100999]
Kim KI; Malakhova OA; Hoebe K; Yan M; Beutler B; Zhang DE. 2005. Enhanced antibacterial potential in UBP43-deficient mice against Salmonella typhimurium infection by up-regulating type I IFN signaling. J Immunol 175(2):847-54. [PubMed: 16002682] [MGI Ref ID J:100695]
Knobeloch KP; Utermohlen O; Kisser A; Prinz M; Horak I. 2005. Reexamination of the role of ubiquitin-like modifier ISG15 in the phenotype of UBP43-deficient mice. Mol Cell Biol 25(24):11030-4. [PubMed: 16314524] [MGI Ref ID J:103758]
Malakhova OA; Yan M; Malakhov MP; Yuan Y; Ritchie KJ; Kim KI; Peterson LF; Shuai K; Zhang DE. 2003. Protein ISGylation modulates the JAK-STAT signaling pathway. Genes Dev 17(4):455-60. [PubMed: 12600939] [MGI Ref ID J:119425]
Rempel LA; Austin KJ; Ritchie KJ; Yan M; Shen M; Zhang DE; Henkes LE; Hansen TR. 2007. Ubp43 gene expression is required for normal Isg15 expression and fetal development. Reprod Biol Endocrinol 5:13. [PubMed: 17381847] [MGI Ref ID J:121928]
Zou W; Kim JH; Handidu A; Li X; Kim KI; Yan M; Li J; Zhang DE. 2007. Microarray analysis reveals that Type I interferon strongly increases the expression of immune-response related genes in Ubp43 (Usp18) deficient macrophages. Biochem Biophys Res Commun 356(1):193-9. [PubMed: 17349616] [MGI Ref ID J:121441]
Health & husbandry
Health & Colony Maintenance Information
Animal Health Reports
Room Number AX11
Colony Maintenance
Breeding & Husbandry When maintaining a live colony, homozygous mice may be bred. The donating investigator reports that homozygous mice on the FVB/N genetic background exhibit none of the severe neurologic disorders that lead to the perinatal lethality observed in homozygotes on a C57BL/6 or mixed B6;129 genetic backgoround. Mating System Homozygote x Homozygote (Female x Male) Diet Information LabDiet® 5K52/5K67
Purchasing information
Pricing, Supply Level & Notes, Controls, General Terms & Conditions
Pricing
| Pricing for USA, Canada and Mexico shipping destinations |
|
Weeks of Age Price* Gender Genotypes Provided Individual Mouse Price $155.70 Female or Male Homozygous for Usp18tm1Dzh *Price(s) in US dollars ($)
Pairs /Price* Pair Genotype $311.40 Homozygous for Usp18tm1Dzh x Homozygous for Usp18tm1Dzh
Additional Supply Details
| Supply Notes |
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| Pricing for International shipping destinations |
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Weeks of Age Price* Gender Genotypes Provided Individual Mouse Price $202.50 Female or Male Homozygous for Usp18tm1Dzh *Price(s) in US dollars ($)
Pairs /Price* Pair Genotype $404.90 Homozygous for Usp18tm1Dzh x Homozygous for Usp18tm1Dzh
Additional Supply Details
| Supply Notes |
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Supply Details
| Standard Supply | Repository-Live. A collection of over 1000 strains maintained as live colonies. Individual colonies are sized to meet current customer demand. Delivery for orders of 10 mice or less ranges on average from one to eight weeks; mice are generally shipped between four to six weeks of age with a maximum shipping age of ~nine weeks. Colony sizes do not generally support stringent age specifications for large volumes of mice; however custom orders and larger quantities of mice are easily arranged. Estimated ship dates for all orders provided within 48 hours of order placement. |
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| Supply Notes |
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Control Information
| Control | ||
|---|---|---|
| 001800 FVB/NJ | ||
| Considerations for Choosing Controls | ||
| USA, Canada and Mexico - Control Pricing Information for Genetically Engineered Mutant Strains. | ||
| International - Control Pricing Information for Genetically Engineered Mutant Strains. | ||
General Terms and Conditions
See Terms of Use
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The Jackson Laboratory has rigorous genetic quality control and mutant gene genotyping programs to ensure the genetic background of JAX® Mice strains as well as the genotypes of strains with identified molecular mutations. JAX® Mice strains are only made available to researchers after meeting our standards. However, the phenotype of each strain may not be fully characterized and/or captured in the strain data sheets. Therefore, we cannot guarantee a strain's phenotype will meet all expectations. To ensure that JAX® Mice will meet the needs of individual research projects or when requesting a strain that is new to your research, we suggest ordering and performing tests on a small number of mice to determine suitability for your particular project.Ordering and Purchasing Information
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| phone: | 207-288-6470 |
| fax: | 207-288-6655 |
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